Shiga toxin (Stx) is a major virulence factor in infection with Stx-producing Escherichia coli (STEC). We developed a series of linear polymers of acrylamide, each with a different density of trisaccharide of globotriaosylceramide (Gb3), which is a receptor for Stx, and identified Gb3 polymers with highly clustered trisaccharides as Stx adsorbents functioning in the gut. The Gb3 polymers specifically bound to both Stx1 and Stx2 with high affinity and markedly inhibited the cytotoxic activities of these toxins. Oral administration of the Gb3 polymers protected mice after administration of a fatal dose of E. coli O157:H7, even when the polymers were administered after the infection had been established. In these mice, the serum level of Stx was markedly reduced and fatal brain damage was substantially suppressed, which suggests that the Gb3 polymers entrap Stx in the gut and prevent its entrance into the circulation. These results indicate that the Gb3 polymers can be used as oral therapeutic agents that function in the gut against STEC infections.

Cyclodextrin derivatives are synthesized as membrane-disrupting agents via a microwave-assisted Huisgen reaction. Their ability to permeabilize bacterial membranes depends on the amino substituents and an appropriate balance of hydrophobicity and hydrophilicity, thus enabling the preparation of derivatives with selective toxicity against bacteria.

Emergence of drug‐resistant bacterial pathogens and the concurrent demand for new antibiotics has led to membrane‐active antimicrobial cyclodextrin (CD) development. CDs contain polyalkylamino groups; molecule polyfunctionalization was achieved via a click reaction. A survey using CDs with systematically varied functionalities clarified the unique correlation of their antimicrobial activity with the molecules’ hydrophobicity/hydrophilicity balance. The optimum hydrophobicity of the membrane‐active molecule was specific to bacterial strains and animal cells, leading to selective toxicity against bacteria including multidrug‐resistant bacteria such as methicillin‐resistant Staphylococcus aureus. The results demonstrate that CDs have a good molecular scaffold to pursue rationally designed structures with a desired activity for new antibiotic development.

We previously developed linear polymers bearing clustered trisaccharides of globotriaosylceramide (Gb3) as orally applicable Shiga toxin (Stx) neutralizers. Here, using a Gb3 polymer with a short spacer tethering the trisaccharide to the core, we found that shortening the spacer length markedly reduced the binding affinity for Stx2 but not Stx1. Moreover, mutational analysis revealed that the essential binding sites of the terminal trisaccharides were completely different between Stx1 and Stx2. These results provide the molecular basis for the interaction between Stx B subunits and Gb3 polymers.

To convert coal fly ash (Fa) into Na-A zeolites, Fa and NaOH-NaAlO 2 solutions were added into the tube made by a semipermeable membrane and aged in the same NaOH-NaAlO 2 solutions at 85 °C for a given period. The amorphous aluminosilicates in Fa were used as Si and Al sources for synthesis of zeolites. The SiO 2 /Al 2 O 3 molar ratio of the starting materials was controlled from 2.0 to 5.0. The amorphous aluminosilicate of Fa completely dissolved during the aging and Pc type zeolite was formed in the tube over the whole range of SiO 2 /Al 2 O 3 . On the other hand, the crystalline phase of Fa, such as R-quartz and mullite, was poorly dissolved. After the mixture was aged for 48 h, white precipitates resulted outside the tube. At SiO 2 /Al 2 O 3 ) 2.0, the precipitates were identified as Na-A zeolite and hydroxysodalite. The Na-X zeolite was produced at SiO 2 /Al 2 O 3 g 2.5 and its crystallinity increased with increasing the molar ratio SiO 2 /Al 2 O 3 , whereas the crystallinity of Na-A zeolite and hydroxysodalite decreased. A singlephase Na-A zeolite was obtained by aging at SiO 2 /Al 2 O 3 ) 2.0 for 24-30 h.